Dose-Ranging Study for Miconazole Oil for Treatment of Otomycosis

• ClinicalTrials.gov Identifier: NCT03130738
• Recruitment Status: Completed
• First Posted: April 26, 2017
• Results First Posted: May 8, 2020
• Last Update Posted: May 8, 2020
• Sponsor: Hill Dermaceuticals, Inc.
• Collaborator: QST Consultations, Ltd.
• Information provided by (Responsible Party): Hill Dermaceuticals, Inc.

Study Description

Brief Summary:

The purpose of the study is to evaluate the efficacy and safety of active treatment (miconazole oil) for 7 versus 14 days, and to compare 14 days of active treatment (miconazole oil) to inactive treatment (placebo) over a 14-day treatment duration, in subjects with fungal infection (otomycosis) of the external ear.

Condition or disease	Intervention/treatment	Phase
Otomycosis	Drug: 7-Day Miconazole Oil (Miconazole 2%); Drug: 14-Day Miconazole Oil (Miconazole 2%); Drug: 14-Day Placebo - Oil Vehicle	Phase 2

Detailed Description:

Miconazole, an imidazole antifungal agent, is commonly used for different types of fungal skin infections, such as Candida, ringworm, jock itch, athlete's foot, nail fungus, vaginal yeast infections, and oropharyngeal candidiasis. The 2% formulation of miconazole is commonly used for dermatophytic infections. The mechanisms of action of miconazole against fungi in general appear to be applicable to fungi associated with otomycosis, in that miconazole has been demonstrated to have activity in vitro against some clinical isolates of fungi associated with human otomycosis in the US.

Miconazole targets the cytochrome P450-dependent enzyme 14-α-sterol demethylase, an enzyme that is also involved in mammalian cholesterol synthesis, resulting in inhibition of ergosterol biosynthesis in the cell membrane of the fungal organism. Because ergosterol is an important component of the cell membrane, inhibition of its synthesis inhibits fungal cell growth.

In addition to its activity toward the enzyme 14-α-sterol demethylase, miconazole also leads to increased reactive oxygen species in fungal organisms, which appears to result in fungicidal activity.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Subjects, investigators, and study staff will not be masked as to the treatment duration assigned to each subject (7 versus 14 days). For subjects receiving the 14-day treatment with study drug, the contents of the study drug (active versus placebo) will be masked to the subject, investigator, and study staff.
• Primary Purpose: Treatment
• Official Title: Dose-Ranging Study of the Efficacy and Safety of Miconazole Oil Used for 7 or 14 Days Compared With Vehicle in the Treatment of Otomycosis
• Actual Study Start Date: April 20, 2017
• Actual Primary Completion Date: August 6, 2019
• Actual Study Completion Date: August 6, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 7-Day Miconazole Oil (Miconazole 2%); 7 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole)	Drug: 7-Day Miconazole Oil (Miconazole 2%); 7 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole); Other Name: Miconazole
Active Comparator: 14-Day Miconazole Oil (Miconazole 2%); 14 days of 2x per day of treatment with Miconazole Oil (Active Drug Product 2% Miconazole)	Drug: 14-Day Miconazole Oil (Miconazole 2%); 14 days of 2x per day treatment with Miconazole Oil (Active Drug Product 2% Miconazole); Other Name: Miconazole
Placebo Comparator: 14-Day Placebo - Oil Vehicle; 14 days of 2x per day of treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient	Drug: 14-Day Placebo - Oil Vehicle; 14 days of 2x per day treatment with Placebo - Oil Vehicle, Study Drug base without active ingredient; Other Name: (Miconazole) Placebo Oil Vehicle

Outcome Measures

Primary Outcome Measures :

1. Primary Efficacy Endpoint [ Time Frame: At Test of Cure visit (Day 15 for 7 Day Active and Day 22 for 14 Day Active and 14 Day Vehicle) ]
   Percentage of subjects in MITT population, at the "Test of Cure" visit with "Therapeutic cure", defined as a negative fungal culture plus "clinical cure" defined as the absence of all otomycosis signs and symptoms for pruritus, debris, fungal elements, and pain.

Secondary Outcome Measures :

1. Secondary Efficacy Endpoints [ Time Frame: At Test of Cure visit (Day 15 for 7 Day Active and Day 22 for 14 Day Active and 14 Day Vehicle) ]
   1. Percentage of subjects in MITT population with clinical cure at the Test of Cure Visit
   2. Percentage of subjects in MITT population with a negative fungal culture at the Test of Cure Visit
   3. Percentage of subjects in MITT population with a negative fungal culture at the Test of Cure visit as well as individual sign or symptom score of 0 or 1 on each of the scales for pruritus and debris and a score of 0 on each of the scales for fungal elements and pain (Secondary therapeutic cure).
   4. Percentage of subjects in MITT population with individual signs or symptoms with a score of 0 or 1 on each of the scales for pruritus and debris and a score of 0 on each of the scales for fungal elements and pain (Secondary clinical cure).

Eligibility Criteria

• Ages Eligible for Study: 25 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Uncomplicated otomycosis of the external ear only, age more than 2 year

Exclusion Criteria:

• Pregnancy
• Other dermatoses or conditions of the ear that may interfere with the evaluation of otomycosis, including concomitant otic infections (including bacterial infection) that require antimicrobial treatment, disease that has spread beyond the external ear(s), or pre-existing skin atrophy of the affected ear(s)
• Tympanostomy tube or perforated tympanic membrane in the ear(s) that will be treated
• Previous surgery affecting the ear(s) that will be treated, except for prior tympanostomy tube(s) that had been removed and had completely healed
• Previous use of medicated treatments for otomycosis or participation in another investigational study within 28 days of study entry
• Previous use of any systemic antifungal therapy, warfarin, and immunosuppressive or immune-stimulating drugs within 28 days of study entry, or systemic steroids within 3 months of study entry
• Recurrent otomycosis that had been unresponsive to previous antifungal treatment
• Known hypersensitivity to any of the components in the test formulation

Contacts and Locations

Locations

United States, California

Head and Neck Surgery Specialist

Chula Vista, California, United States, 91910

University of California San Diego

La Jolla, California, United States, 92037-0970

United States, Florida

Ear Nose and Throat Associates of Southe Florida

Boynton Beach, Florida, United States, 33426

Silverstein Institute

Sarasota, Florida, United States, 34239

United States, Kentucky

Advanced ENT and Allergy

Louisville, Kentucky, United States, 40207

United States, North Carolina

Piedmont ENT Associates

Winston-Salem, North Carolina, United States, 27103

Sponsors and Collaborators

Hill Dermaceuticals, Inc.

QST Consultations, Ltd.

Investigators

• Study Director: Rosario G Ramirez, MD; Hill Dermaceuticals, Inc.
• Principal Investigator: Jack Wazen, MD; Silverstein Institute
• Principal Investigator: Quyen T Nguyen, MD; UCSD
• Principal Investigator: Kenneth Hodge, MD; Advanced ENT and Allergy
• Principal Investigator: Kenneth S Maxwell, MD; Piedmont Ear, Nose and Throat Associates
• Principal Investigator: Woo Linda, MD; Head and Neck Surgery Specialists

  Study Documents (Full-Text)

Documents provided by Hill Dermaceuticals, Inc.:

Study Protocol  [PDF] April 17, 2019

Statistical Analysis Plan  [PDF] May 30, 2019

More Information

• Responsible Party: Hill Dermaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03130738
• Other Study ID Numbers: HD-MCZ-PHII-DRF062016
• First Posted: April 26, 2017
• Results First Posted: May 8, 2020
• Last Update Posted: May 8, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Otomycosis; Mycoses; Bacterial Infections and Mycoses; Infections; Ear Diseases; Otorhinolaryngologic Diseases; Miconazole; Clotrimazole; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Anti-Infective Agents, Local